Processes for preparing sterol esters

ABSTRACT

A food additive useful for lowering serum cholesterol in humans contains a sterol or stanol ester of a fatty acid or a dicarboxylic acid ester of a sterol or stanol made by reacting a sterol, stanol and a carboxylic acid in the presence of an effective amount of a catalyst selected from the group consisting of calcium oxide, calcium hydroxide, a calcium salt of a carboxylic acid, magnesium hydroxide and combinations thereof described herein below.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. §120, and is adivisional application of, U.S. patent application Ser. No. 09/083,584,filed May 21, 1998 (now U.S. Pat. No. 6,394,230); which is acontinuation-in-part of U.S. patent application Ser. No. 09/072,434,filed May 4, 1998 (now abandoned), which in turn claimed priority under35 U.S.C. §119(e), of U.S. Provisional Patent Application No.60/069,790, filed Dec. 16, 1997 (now expired), the entire contents ofeach of the aforementioned patent applications being incorporated hereinby reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

BACKGROUND OF THE INVENTION

Phytosterols have been found to be effective in reducing serumcholesterol in humans. Phytosterols are steroids that bear a closestructural relationship to cholesterol but differ in the configurationof the side chains at the 17-position. It is well known thatβ-sitosterol and the fatty acid esters of β-sitosterol are effective inreducing serum cholesterol. Recent studies have found that β-sitostanoland the fatty acid esters of β-sitostanol are particularly effective inreducing serum cholesterol and LDL levels. It has been recently reportedthat the fatty acid esters of β-sitostanol are particularly effectivecholesterol-reducing agents presumably because they are in solution.Such esters can be introduced into the body as additives in foodproducts such as margarine. Margarines containing β-sitosterol and thosecontaining β-sitosterol fatty acid esters as well as margarinescontaining β-sitostanol and β-sitostanol fatty acid esters have beenshown to reduce serum cholesterol levels in humans.

BRIEF SUMMARY OF THE INVENTION

The present invention pertains to a food additive containing a sterol orstanol ester of a fatty acid or a dicarboxylic acid ester of a sterol orstanol made by the process described herein below. The food additive canbe incorporated into food for the purpose of lowering serum cholesterolin humans and/or for reducing the absorption of cholesterol from foodsand/or beverages. The food additive is prepared by combining a steroland/or stanol fatty acid ester thereof and/or a dicarboxylic acid esterof a sterol or stanol made by the process described herein and an ediblesolubilizing agent, an effective amount of a suitable antioxidant and aneffective amount of a suitable dispersant. The sterol and/or stanolesters made by the process described herein can be used without removingthe catalyst because the catalyst is non-toxic and used at low levels.Another advantage is that when the fatty acid esters of sterols orstanols are prepared by transesterification, the ester that istransesterified can be either a lower alkyl ester such as a methyl or anethyl ester or a triglyceride which is a triglyceryl ester of a C₆₋₂₂fatty acid such as a conventional fat or oil.

Another aspect of the invention pertains to a method of reducing theabsorption of cholesterol into the bloodstream which comprises orallyintroducing into the body an effective amount of a substance containinga β-sitostanol ester made by reacting a stanol and a carboxylic acid inthe presence of an effective amount of a catalyst selected from thegroup consisting of calcium oxide, calcium hydroxide, a calcium salt ofa carboxylic acid, magnesium hydroxide and combinations thereof.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

Not Applicable.

DETAILED DESCRIPTION OF THE INVENTION

The term sterol is well known to those skilled in the art and generallyrefers to those compounds having a perhydrocyclopentanophenanthrene ringsystem (the ring system depicted in Formula III herein) and having oneor more OH substituents, examples of which include, but are not limitedto, cholesterol, campesterol, ergosterol, sitosterol, and the like. Itis common to obtain sterols as mixtures of compounds such as, forexample, GENEROL® 122N sterols, a trademark product of HenkelCorporation, Gulph Mills, Pa. GENEROL® 122N sterol contains 25-30%campesterol, 17-22% stigmasterol and 45-50% sitosterol.

The term stanol is well known to those skilled in the art and generallyrefers to those compounds having a saturatedperhydrocyclopentanophenanthrene ring system (the ring system depictedin Formula II herein) and having one or more OH substituents, examplesof which include, but are not limited to, campestanol, sitostanol whichalso known as β-sitostanol and stigmastanol, coprostanol, cholestanoland the like.

The food additive according to the invention is comprised of a steroland/or stanol ester of a fatty acid wherein the ester is made byreacting a sterol and/or stanol with a fatty acid having from 6 to 22carbon atoms in the presence of an effective amount of a catalystselected from the group consisting of calcium oxide, calcium hydroxide,a calcium salt of a carboxylic acid, magnesium hydroxide andcombinations thereof or a dicarboxylic acid ester of a sterol or stanolof the formula I. Since the catalyst is non-toxic and used at lowlevels, the sterol and/or stanol ester of the fatty acid can be addeddirectly to foods without further processing such as removal of thecatalyst. The sterol can be any sterol. Examples of suitable sterolsinclude, but are not limited to, campesterol, ergosterol, stigmasterol,sitosterol or a combination thereof. A preferred sterol is β-sitosterol.A commercially available combination of sterols is GENEROL® 122N sterolsas set forth herein. The stanol can be any stanol. Examples of suitablestanols include, but are not limited to, campestanol, sitostanol whichis also known as β-sitostanol and stigmastanol, coprostanol, cholestanoland the like. A preferred stanol is β-sitostanol.

The amount of sterol and/or stanol fatty acid ester that can be used inthe food additive is an effective amount which is any amount necessaryto either reduce serum cholesterol in humans after ingestion of a foodcontaining the food additive or an amount necessary to reduce theabsorption of cholesterol from foods and/or beverages. A preferred foodadditive composition of the instant invention comprises from about 70%to about 80% vegetable oil, from about 1% to about 2% tocopherols, andfrom about 10% to about 25% sterol and/or stanol fatty acid esterprepared by the method according to the invention.

The food additive is prepared by combining a sterol and/or stanol esterof a fatty acid made by the process described herein and an ediblesolubilizing agent, an effective amount of a suitable antioxidant and aneffective amount of a suitable dispersant. The solubilizing agent can bevegetable oil such as, for example, sunflower oil, palm kernel oil,coconut oil, rape seed oil, tallow, corn oil, canola oil, linseed oil,palm oil, olive oil, sesame oil, safflower oil, and the like,monoglycerides, diglycerides, triglycercides, tocopherols, and the like,and mixtures thereof. The antioxidant can be ascorbic acid (Vitamin C),tocopherols such as α-tocopherol (vitamin E), β-carotene, an extract ofthe bark of the maritime pine, Pinus maritima and combinations thereof.The extract of the bark of the maritime pine, also known as PYCNOGENOL™,contains procyanidines consisting of catechin and epicatechin unitslinked by C—C bonds to form dimers, trimers and other oligomers up to achain length of 6-7 molecules and phenolic acids and its glucosederivatives. PYCNOGENOL™ is produced according to U.S. Pat. No.4,698,360, which is incorporated herein for reference. The extract usedaccording to the invention may be prepared essentially by extractingmaritime pine bark in comminuted form with boiling water, saturating thefiltered extract with sodium chloride or, alternatively, adding ammoniumsulfate to 20% w/v, separating the precipitate formed, repeatedlyextracting the supernatant with 1/10 volume of ethyl acetate, drying thecollected ethyl acetate extracts, concentrating the dried extract,pouring it into 3 volumes of chloroform with stirring and collecting theprecipitate which may be purified by repeating the dissolution in ethylacetate and precipitation with chloroform. Mixtures of the aboveantioxidants can also be used.

A suitable dispersant is any biologically acceptable surface activeagent, examples of which include, but are not limited to, an alkylpolyglycoside, lecithin, polysorbate 80, sodium lauryl sulfate, and thelike. The alkyl polyglycosides which can be used in the invention havethe formula V

R₁O(R₂O)_(b)(Z)_(a)  V

wherein R₁ is a monovalent organic radical having from about 6 to about30 carbon atoms; R₂ is a divalent alkylene radical having from 2 to 4carbon atoms; Z is a saccharide residue having 5 or 6 carbon atoms; b isa number having a value from 0 to about 12; a is a number having a valuefrom 1 to about 6. Preferred alkyl polyglycosides which can be used inthe compositions according to the invention have the formula I wherein Zis a glucose residue and b is zero. Such alkyl polyglycosides arecommercially available, for example, as APG®, GLUCOPON®, PLANTAREN® orAGRIMUL® surfactants from Henkel Corporation, Ambler, Pa., 19002.Examples of such surfactants include but are not limited to:

1. GLUCOPON® 220 Surfactant—an alkyl polyglycoside in which the alkylgroup contains 8 to 10 carbon atoms and having an average degree ofpolymerization of 1.5.

2. GLUCOPON® 225 Surfactant—an alkyl polyglycoside in which the alkylgroup contains 8 to 10 carbon atoms and having an average degree ofpolymerization of 1.7.

3. GLUCOPON® 600 Surfactant—an alkyl polyglycoside in which the alkylgroup contains 12 to 16 carbon atoms and having an average degree ofpolymerization of 1.4.

4. GLUCOPON® 625 Surfactant—an alkyl polyglycoside in which the alkylgroup contains 12 to 16 carbon atoms and having an average degree ofpolymerization of 1.4.

5. APG® 325 Surfactant—an alkyl polyglycoside in which the alkyl groupcontains 9 to 11 carbon atoms and having an average degree ofpolymerization of 1.6.

6. PLANTAREN® 2000 Surfactant—an alkyl polyglycoside in which the alkylgroup contains 8 to 16 carbon atoms and having an average degree ofpolymerization of 1.4.

7. PLANTAREN® 1300 Surfactant—an alkyl polyglycoside in which the alkylgroup contains 12 to 16 carbon atoms and having an average degree ofpolymerization of 1.6.

8. AGRIMUL® PG 2067 Surfactant—an alkyl polyglycoside in which the alkylgroup contains 8 to 10 carbon atoms and having an average degree ofpolymerization of 1.7.

Other examples include alkyl polyglycoside surfactant compositions whichare comprised of mixtures of compounds of formula I as described in U.S.Pat. Nos. 5,266,690 and 5,449,763, the entire contents of both of whichare incorporated herein by reference.

The method by which the novel food additive composition is used toreduce cholesterol absorption from foods and beverages includes the stepof commingling the food additive composition with foods and beverages,mixing until uniformly blended. The novel food additive is effective asan additive in margarine, cooking oils or shortening for the purpose ofreducing serum cholesterol in humans who ingest food products made withthe novel additive. Margarine containing the novel food additive can bemade by methods well known to those skilled. A general method for makingmargarine is disclosed in pages 77-84 of Volume 3 of Bailey's IndustrialOil and Fat Products (1985), the entire contents of which areincorporated herein by reference. The amount of sterol and/or stanolfatty acid ester useful in the novel food additive is an effectiveamount which is any amount necessary to either reduce serum cholesterolin humans after ingestion of a food containing the food additive or anamount necessary to reduce the absorption of cholesterol from foodsand/or beverages. A preferred food additive composition of the instantinvention comprises from about 70% to about 80% vegetable oil, fromabout 1% to about 2% tocopherols, and from about 10% to about 25% steroland/or stanol fatty acid ester prepared by the method according to theinvention. Particularly preferred compositions are composed of fromabout 70% to about 80% sunflower oil and/or rape seed oil, from about 1%to about 2% vitamin E and/or an extract of the bark of the maritimepine, Pinus maritima and from about 10% to about 25% of a sterol and/orstanol fatty acid ester prepared by the method according to theinvention.

Another aspect of the invention pertains to a method of reducing theabsorption of cholesterol into the bloodstream which comprises orallyintroducing into the body an effective amount of a substance containinga β-sitostanol ester made by reacting β-sitostanol and a carboxylic acidin the presence of an effective amount of a catalyst selected from thegroup consisting of calcium oxide, calcium hydroxide, a calcium salt ofa carboxylic acid, magnesium hydroxide and combinations thereof. Thecholesterol-lowering ability of fatty acid esters of β-sitostanol isdescribed in U.S. Pat. No. 5,502,045, the entire contents of which areincorporated herein by reference. The fatty acid esters of β-sitostanolmade by the process described herein can be orally introduced byingesting food products containing the food additives of the presentinvention. Preferred methods of oral introduction of the β-sitostanolmade by the process described herein is through the ingestion ofmargarine, cooking oils or shortening containing a food additiveaccording to the invention. A particularly effective amount ofβ-sitostanol fatty acid esters is from about 0.2 to about 20 grams perday. Particularly preferred additives are composed of from about 70% toabout 80% sunflower oil and/or rape seed oil, from about 1% to about 2%vitamin E and/or an extract of the bark of the maritime pine, Pinusmaritima and from about 10% to about 25% of a β-sitostanol fatty acidester prepared by the method according to the invention.

In regard to the esterification process used to make the sterol and/orstanol esters which can be used in the novel food additive, anyaliphatic, cycloaliphatic, or aromatic mono- or poly-carboxylic acidhaving at least 2 carbon atoms or mixtures of such acids can be used inthe process according to the invention. Examples of aliphaticmono-carboxylic acids include, but are not limited to acetic, propionic,valeric, pelargonic, palmitic, lauric, oleic, linoleic acid, and thelike. Examples of cycloaliphatic mono-carboxylic acids include, but arenot limited to cyclopentane carboxylic acid, cyclohexane carboxylicacid, cyclohexene carboxylic acid and the like. Examples of aromaticmono-carboxylic acids include, but are not limited to benzoic acid,toluic acid, aminobenzoic acid and the like. Examples of aliphaticpoly-carboxylic acids include, but are not limited to oxalic, malonic,adipic, azelaic acid, C-36 dimer acid, citric acid and the like.Examples of aromatic poly-carboxylic acids include, but are not limitedto phthalic acid, trimellitic acid and the like. Preferred carboxylicacids are mixtures of long chain carboxylic acids such as those derivedfrom naturally occurring oils such as sunflower oil, palm kernel oil,coconut oil, rape seed oil, tallow, corn oil, canola oil, linseed oil,palm oil, olive oil, sesame oil, safflower oil, and the like which areknown to those skilled in the art and are disclosed in chapter 6 ofVolume 1 of the fourth edition (1979) of Bailey's Industrial Oil and FatProducts, the entire contents of which are incorporated herein byreference. Preferred fatty acid mixtures are those obtained fromsunflower oil and rape seed oil.

The direct or transesterification modifications of the esterificationprocesses can be carried out in the presence of a calcium oxide, calciumhydroxide, a calcium salt of a carboxylic acid, magnesium hydroxidecatalyst or a combination of such catalysts. One advantage of the methodaccording to the invention is that the calcium or magnesium catalystscan be left in the product or removed by contacting the reaction productwith a chelating agent such as L-tartaric acid or EDTA. The preferredcatalysts are calcium hydroxide, calcium oxide and the calcium salt of afatty acid having from about 10 to about 22 carbon atoms. Calcium oxideis a particularly preferred catalyst. The amount that can be used is aneffective amount which is any amount required to effect the conversionof a sterol or stanol to the corresponding ester. Typically, the amountwill range from about 0.01% to 0.2% based on the total weight of thereaction mixture and will preferably be in the range of about 0.02% toabout 0.05%.

The processes according to the invention can be carried out at atemperature in the range of from about 190° C. to about 210° C. Thetemperature for a particular reaction will depend upon a number offactors such as the nature of the catalyst, the equipment in which thereaction is carried out and whether a sterol or stanol is esterified ortransesterified. If a sterol is used in the process according to theinvention, a temperature in the range of 190° C. to about 210° C. isoptimum. Such a temperature will minimize the dehydration of the sterol.If a stanol is used in the process according to the invention, atemperature up to about 210° C. is optimum.

The transesterification process according to the invention can becarried out using any type of carboxylic acid ester. Such esters includesimple esters such as lower alkyl esters which include, for example,methyl, ethyl, propyl, or butyl esters or higher alkyl esters such aspentyl, hexyl, heptyl and the like or triglycerides which aretriglyceryl esters of C₆₋₂₂ fatty acids such as conventional fats oroils. The transesterification conditions will vary according to the typeof ester employed. If a glyceride is used, the temperature will be inthe range of from about 210° C. to about 250° C., preferably from about220° C. to about 230° C. If an ester of a lower molecular weight alcoholis used such as a methyl or ethyl ester such that the alcohol formedwill be readily removed under the reaction conditions as, opposed to theuse of a triglyceride where the glycerin formed is not as readilyremoved, the temperature will be in the range of from about 100° C. toabout 130° C., preferably from about 110° C. to about 120° C.

The direct esterification process according to the invention can becarried out by mixing the reactants in a batch reactor and heating thereactor contents to an appropriate temperature to remove the water ofreaction. This may be accomplished at atmospheric pressure or below.Another method of carrying out the process according to the invention isto pass the reaction mixture through an evaporator such as a thin filmevaporator or wiped film evaporator operating at a pressure of about 2-3millibars and at a temperature of about 230° C. while the reaction istaking place or after the reaction has been completed. It is preferableto operate the evaporator using an inert gas or vapor such as nitrogenor steam such that the inert gas or vapor contacts the thin film ofreaction mixture in a counter-current fashion. The reaction mixture ispassed through the evaporator one or more times in order to increase thesurface to volume ratio to more efficiently remove the water of reactionthereby decreasing the time the reaction mixture spends at elevatedreaction temperatures. One embodiment of the aforementioned method is acombination of a stirred tank reactor and an evaporator wherein thereactants are heated to reaction temperature and then repeatedlycirculated through the evaporation means. An advantage of carrying outthe process according to the invention on a commercial scale is thatsince no low molecular weight alcohol is produced as in, for example,transesterification of a methyl ester, there is no foaming in a reactordue to the evolution of the low molecular weight alcohol such asmethanol. Therefore, the full working volume of the reactor can beutilized without an allowance for foam volume.

The process according to the invention is particularly useful for thepreparation of dicarboxylic acid esters of sterols and/or stanolswherein the dicarboxylic acids are fully esterified or partiallyesterified. Such compounds have the formula I

wherein R¹ is an aliphatic or aromatic moiety having from one to about36 carbon atoms. Examples of possible values of R¹ include, but are notlimited to, branched and unbranched alkylene and alkenylene radicalshaving from 2 to 18 carbon atoms; dimer acid residues which arecycloaliphatic moieties having 34 carbon atoms; aromatic radicals andeach of R² and R³ is hydrogen, or a radical of the formula II or formulaIII

wherein R⁴ is an alkyl, substituted alkyl, alkenyl or substitutedalkenyl group having from one to about 10 carbon atoms; each of R² or R³is independently hydrogen with the proviso that only one of R² or R³ canbe hydrogen. In the instances where only one of R² or R³ is hydrogenrefer to the partial or half esters of the dicarboxylic acids. Thesecompounds are useful as for reducing serum cholesterol and LDL levels.Preferred compounds of the formula I include those wherein R¹ is analkylene radical having from 2 to 18 carbon atoms with alkylene radicalshaving 7, 8, 10, and 11 carbons being especially preferred; each of R²and R³ is a radical of the formula II wherein R⁴ is an alkyl radicalhaving from 2 to 10 carbon atoms. Preferred values of R⁴ include abranched alkyl group having 10 carbon atoms. A most preferred R⁴ is analkyl group of the formula IV

Most preferred compounds of the formula I include the disitostanol esterof azelaic acid, the disitostanol ester of brassylic acid, thedisitostanol ester of decanedioic acid, the disitostanol ester ofdodecanedioic acid, the disitosterol ester of azelaic acid, thedisitosterol ester of brassylic acid, the disitostanol ester ofdecanedioic acid and, the disitosterol ester of dodecanedioic acid, thesitostanol monoester of azelaic acid, the sitostanol monoester ofbrassylic acid, the sitostanol monoester of decanedioic acid, thesitostanol monoester of dodecanedioic acid, the sitosterol monoester ofazelaic acid, the sitosterol monoester of brassylic acid, the sitostanolmonoester of decanedioic acid and, the sitosterol monoester ofdodecanedioic acid.

The following examples are meant to illustrate but not to limit theinvention.

EXAMPLE 1

About 250 grams of sunflower fatty acid (acid value=200.1) was added toa clean, dry vessel under nitrogen, heated to 130° C. with agitation andnitrogen sparge. About 357 grams of mixed stanols (hydrogenated GENEROL®122N sterol ) was added at a rate slow enough to avoid cooling whileagitating with a nitrogen sparge. This required about one half hour.After the addition of the stanol, 0.34 grams of calcium hydroxide wasadded and the pressure was gradually decreased to 27 inches, while thetemperature was increased to 230° C. After six hours, the pressure wasreduced to 40 mm Hg while maintaining the heat at 230° C. for anothersix hours. The reaction mixture was cooled under vacuum and the vacuumbroken with nitrogen. The acid value at this point was 7.4. A solutionof 2.7 grams of tartaric acid in 20 ml water was added to the crudeproduct at 80° C. with agitation and nitrogen sparge. The mixture wasthen heated to 110° C. and 27 inches vacuum for a half hour to removewater. TONSIL® Optimum FF bleaching clay was then added under nitrogen,the mixture agitated for a half hour and filtered through a bed ofCELITE® filter aid on a heated Buchner funnel. The batch lightened uponneutralization of the catalyst and filtration.

Analysis

Appearance

Clear yellow liquid which sets up to a wax

Color (Gardner): 5

Acid Value: 7.35

% Stanol: 4.4

Ppm Calcium: 1

EXAMPLE 2

About 250 grams of sunflower fatty acid (acid value=200.1) was added toa clean, dry vessel under nitrogen, heated to 130° C. with agitation andnitrogen sparge. About 357 grams of mixed sterols (GENEROL® 122N sterol)was added at a rate slow enough to avoid cooling while agitating with anitrogen sparge. This required about one half hour. After the additionof the stanol, 0.34 grams of calcium oxide was added and the pressurewas gradually decreased to 27 inches, while the temperature wasincreased to 210° C. After six hours, the pressure was reduced to 40 mmHg while maintaining the heat at 230° C. for another six hours. Thereaction mixture was cooled under vacuum and the vacuum broken withnitrogen. The acid value at this point was 7.4. A solution of 2.7 gramsof tartaric acid in 20 ml water was added to the crude product at 80° C.with agitation and nitrogen sparge. The mixture was then heated to 110°C. and 27 inches vacuum for a half hour to remove water. TONSIL® OptimumFF bleaching clay was then added under nitrogen, the mixture agitatedfor a half hour and filtered through a bed of CELITE® filter aid on aheated Buchner funnel. The batch lightened upon neutralization of thecatalyst and filtration.

EXAMPLE 3

A dicarboxylic ester is made by reacting one mole of a sterol or stanolwith a ½ mole of a dicarboxylic acid in the presence of calcium oxide at210 degrees under reduced pressure according to the procedure ofExamples 1 and 2 above.

EXAMPLE 4

About 312 grams of sunflower fatty acid (acid value =200.1) was added toa clean, dry vessel under nitrogen, heated to 120° C. with agitation andnitrogen sparge. About 357 grams of GENEROL® 122N sterol was added at arate slow enough to avoid cooling while agitating with a nitrogensparge. This required about one half hour. After the addition of theGENEROL® 122N, 0.34 grams of calcium oxide was added and the pressurewas gradually decreased to 30 mbar while the temperature was increasedto 210° C. After six hours at 210° C. and <30 mbar, the reaction mixturewas cooled under vacuum, and the acid value at this point was 22.2. Asolution of 3.72 g tartaric acid in 23 g water was added to the crudeproduct at 80° C. with agitation and nitrogen sparge. The mixture wasthen heated to 90° C. and 17 mbar for one hour. The vacuum was releasedwith nitrogen, added 2 g of TONSIL® FF, 1.4 g of Clarcel DICB, evacuatedto <30 mbar and filtered at 90° C. The batch lightened uponneutralization of the catalyst and filtration. The crude productcontained 4.7% unreacted sterol via GC analysis.

What is claimed is:
 1. A process for preparing an ester, said processcomprising reacting at least one first reactant selected from the groupconsisting of sterols, stanols, and combinations thereof with at leastone second reactant selected from the group consisting of carboxylicacids and carboxylic acid esters in the presence of a catalyticallyeffective amount of a catalyst selected from the group consisting ofcalcium oxide, calcium hydroxide, a calcium salt of a carboxylic acid,magnesium hydroxide and combinations thereof.
 2. The process accordingto claim 1, wherein the at least one first reactant comprisesβ-sitosterol.
 3. The process according to claim 1, wherein the at leastone first reactant comprises β-sitostanol.
 4. The process according toclaim 1, wherein the catalyst comprises calcium hydroxide, calcium oxideor a calcium salt of a carboxylic acid.
 5. The process according toclaim 1 , wherein the at least one second reactant comprises acarboxylic acid having from about 2 to 22 carbon atoms.
 6. The processaccording to claim 1, wherein the catalyst comprises calcium oxide. 7.The process according to claim 1, wherein the at least one secondreactant comprises a mixture of long chain carboxylic acids derived froman oil selected from the group consisting of sunflower oil, palm kerneloil, coconut oil, rape seed oil, tallow oil, corn oil, canola oil,linseed oil, palm oil, olive oil, sesame oil, and safflower oil.
 8. Theprocess according to claim 1 , wherein a reaction mixture comprising theat least one first reactant, the at least one second reactant and thecatalytically effective amount of the catalyst is reacted in a reactionzone; and passing at least a portion of the reaction mixture through anevaporation zone to remove the water of reaction from the reactionmixture.
 9. The process according to claim 8, further comprisingreturning the portion of the reaction mixture to the reaction zone. 10.The process according to claim 8, wherein the catalyst comprises calciumoxide.
 11. The process according to claim 1 , wherein the at least onesecond reactant comprises a carboxylic acid ester.
 12. The processaccording to claim 11, wherein the at least one first reactant comprisesβ-sitosterol.
 13. The process according to claim 11, wherein the atleast one first reactant comprises β-sitostanol.
 14. The processaccording to claim 11, wherein the catalyst comprises calcium hydroxide,calcium oxide or a calcium salt of a carboxylic acid.
 15. The processaccording to claim 14, wherein the at least one second reactantcomprises a carboxylic acid ester having from about 2 to 22 carbonatoms.
 16. The process according to claim 14, wherein the at least onesecond reactant comprises a methyl ester of a C₆₋₂₂ fatty acid or atriglyceride.
 17. A process which comprises reacting β-sitostanol with acarboxylic acid ester in the presence of an effective amount of calciumoxide.
 18. A process for making a food additive composition, saidprocess comprising: (a) providing an edible solubilizing agent; (b)providing an effective amount of a suitable dispersant; (c) providing anester prepared by reacting at least one first reactant selected from thegroup consisting of sterols, stanols, and combinations thereof with atleast one second reactant selected from the group consisting ofcarboxylic acids and carboxylic acid esters in the presence of acatalytically effective amount of a catalyst selected from the groupconsisting of calcium oxide, calcium hydroxide, a calcium salt of acarboxylic acid, magnesium hydroxide and combinations thereof; and (d)combining the edible solubilizing agent, the suitable dispersant and theester.
 19. The process according to claim 18, further comprisingproviding an antioxidant and combining the antioxidant with the ediblesolubilizing agent, the suitable dispersant and the ester.